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A model of the ternary complex of interleukin-10 with its soluble receptors

Sergei Pletnev1, Eugenia Magracheva, Alexander Wlodawer

  • 1Macromolecular Crystallography Laboratory, Center for Cancer Research, National Cancer Institute at Frederick, Frederick, MD 21702-1201, USA. svp@ncifcrf.gov

BMC Structural Biology
|June 30, 2005
PubMed

Insights

Interleukin-10 (IL-10) signaling involves a ternary complex with IL-10R1 and IL-10R2. Homology modeling revealed the structure of this complex, identifying key interactions for immune suppression.

Area of Science:

  • Immunology
  • Structural Biology
  • Biochemistry

Background:

  • Interleukin-10 (IL-10) is a cytokine that suppresses immune responses.
  • IL-10 signaling requires a ternary complex of IL-10 with its receptor chains, IL-10R1 and IL-10R2.
  • Low affinity of IL-10R2 has hindered structural studies of the ternary complex.

Purpose of the Study:

  • To determine the structure of the IL-10 ternary complex.
  • To identify residues involved in ligand-receptor and receptor-receptor interactions.
  • To understand the mechanism of IL-10-mediated immune suppression.

Main Methods:

  • Homology modeling was used to generate the structures of the soluble IL-10 receptor chain 2 (sIL-10R2) and the IL-10/sIL-10R1/sIL-10R2 ternary complex.
  • Analysis of the modeled structures to identify interaction sites and types.

Main Results:

  • The structure of the IL-10/sIL-10R1 binary complex is conserved within the ternary complex.
  • Two binding sites for sIL-10R2 exist on the IL-10/sIL-10R1 complex, involving both IL-10 and sIL-10R1.
  • Interactions are predominantly hydrophilic with internal hydrophobic clusters; C-termini are 25 A apart.

Conclusions:

  • The modeled ternary complex structure likely represents the biologically active signaling complex.
  • This structure provides insights into IL-10 receptor interactions and signal transduction.
  • Understanding these interactions is crucial for developing therapies targeting IL-10 signaling.
Abstract

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